The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS.
Spi-1/PU.1 is an Ets protein deregulated by insertional mutagenesis during the murine Friend erythroleukemia. The overexpression of the normal protein in a proerythroblastic cell prevents its terminal differentiation. In normal hematopoiesis Spi-1/PU.1 is a transcription factor that plays a key role in normal myeloid and B lymphoid differentiation. Moreover, Spi-1/PU.1 binds RNA and interferes in vitro with the splicing process. Here we report that Spi-1 interacts in vivo with TLS (translocated in liposarcoma), a RNA-binding protein involved in human tumor-specific chromosomal translocations. This interaction appears functionally relevant, since TLS is capable of reducing the abilities of Spi-1/PU.1 to bind DNA and to transactivate the expression of a reporter gene. In addition, we observe that TLS is potentially a splicing factor. It promotes the use of the distal 5' splice site during the E1A pre-mRNA splicing. This effect is counterpoised in vivo by Spi-1. These data suggest that alteration of pre-mRNA alternative splicing by Spi-1 could be involved in the transformation of an erythroblastic cell.
Hallier
M
M
INSERM U 248, Institut Curie, 26, rue d'Ulm, 75248 Paris Cedex 05, France.
Lerga
A
A
Barnache
S
S
Tavitian
A
A
Moreau-Gachelin
F
F
D017398:Alternative Splicing; D000818:Animals; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011518:Proto-Oncogene Proteins; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1